·

Dennis R. Grayson

Professor of Molecular Neuroscience

Dr. Grayson has been interested in mechanisms associated with gene expression for over 20 years. He joined the laboratory of Dr. James E. Darnell, Jr. at the Rockefeller University on 1984 to study cell-type specific transcription factors. This led to the identification of HNF3A as a hepatocyte nuclear factor important for activating the expression of multiple genes in hepatocytes. In 1988, Dr. Grayson joined the Fidia-Georgetown Institute for the Neurosciences and with the support of Dr. Erminio Costa, initiated a program in studying gene expression in neurons. From 1994-1998, he moved to the Allegheny University of the Health Sciences in Pittsburgh and developed a program in molecular psychiatry. He continued his interests in psychiatry and joined the Psychiatric Institute in 1998. This represented a unique opportunity to join his long time collaborators, Drs. Costa and Guidotti to pursue molecular underpinnings of schizophrenia. Dr. Grayson has received NRSA post-doctoral support, R01 and K04 funding from the NIH over the years. He has published over 100 papers in peer-reviewed journals and actively reviews NIH grants and post-doctoral fellowships. In addition, Dr. Grayson has been invited to speak at numerous national and international meetings.

Interests:

Dr. Grayson’s research interests include understanding the role of DNA methylation in modulating gene expression and the role that this epigenetic regulation may play in the pathophysiology of schizophrenia. While DNA methylating enzymes such as DNMT1 and DNMT3a are abundant in post-mitotic neurons, it is not clear whether methylation acts as a reversible switch to turn on and off genes and how this process varies between functionally distinct neuronal phenotypes. For example, which promoters are affected by changes in methylation in GABAergic interneurons vs. glutamatergic pyramidal neurons. Histone deacetylases (HDACs) are a class of histone modifying proteins associated with chromatin remodeling and gene silencing. HDAC inhibitors reverse this process and differentially activate gene expression in cell-type specific patterns. What determines whether a specific promoter will be expressed in response to different inhibitors and in which type of neuron? These questions are relevant to cognitive performance and behaviors relevant to psychiatric disease.

Affiliations/Memberships:

Society for Neuroscience, Society for Biological Psychiatry, American Society for Biochemistry and Molecular Biology

Projects:

Identification of HDAC inhibitors that might prove therapeutically efficacious in the treatment of cognition in schizophrenia and Alzheimer’s disease; generation of a conditional mutant mouse that overexpresses DNMT1 and DNMT3a in GABA neurons of the brain; role of DNA methylation in the regulation of genes down-regulated in schizophrenia.